Efficacy and Safety Study of Intranasal Administration of 100, 200, and 400 μg of Fluticasone Propionate Using a Novel Bi-directional Device

Subjects reported nasal symptoms using the electronic diary twice daily immediately before dosing. 0: None 1. Mild, symptoms clearly present, but minimal awareness, and easily tolerated 2. Moderate, definite awareness of symptoms that is bothersome but tolerable 3. Severe, symptoms that are hard to tolerate, cause interference with activities or daily living During the single-blind run-in phase and during the 16-week, double-blind treatment phase, an electronic diary was provided to each subject. Subjects reported both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptoms severity over the previous 12 hours) scores for nasal congestion/obstruction symptoms.

Time frame: Baseline, Week 4 of the double-blind treatment phase

Population: The Full Analysis Set includes subjects who received at least one dose of study drug and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

Determined by a nasal polyp grading scale score (sum of scores from both nasal cavities) measured by nasoendoscopy

Time frame: Baseline, Week 16 of the double-blind treatment phase

Population: The Full Analysis Set includes subjects who received at least one dose of study drug and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

Change from baseline in rhinorrhea symptoms, as measured by AM and PM diary symptom scores

Time frame: Baseline, Week 16 of the double-blind treatment phase

Population: Missing data were imputed using the multiple imputation method in the primary analyses for the co-primary efficacy variables. For other efficacy analyses, missing or invalid values were not imputed.

Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate Determined by a nasal polyp grading scale score (sum of scores from both nasal cavities measured by nasoendoscopy)

Time frame: Baseline, Week 24 of the open-label extension phase

Population: The Full Analysis Set includes subjects who received at least one dose of study drug and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

Change from baseline in facial pain/pressure symptoms, as measured by AM and PM diary symptom scores

Time frame: Week 16 of the double-blind treatment phase

Change from baseline in hyposmia symptoms, as measured by AM and PM diary symptom scores

Time frame: Week 16 of the double-blind treatment phase

The MOS Sleep-R is a brief, self-administered, validated questionnaire designed to measure key aspects of sleep, such as disturbance, adequacy, somnolence, and quantity. The 12-item version with a 4-week recall was used in this study. The score range for the 12-item version is 0 to 100, lower scores indicating better sleep and higher scores indicating worse sleep. The scale yields a Sleep Problem Index and scores on the following 6 subscales: Sleep Disturbance, Snoring, Shortness of Breath or Headache, Sleep Adequacy, Sleep Somnolence, and Sleep Quantity.

Time frame: Baseline, Week 16 of the double-blind treatment phase

Measured by the 7-day average instantaneous morning diary symptom scores

Time frame: Week 16 of the double-blind treatment phase

Population: The Full Analysis Set includes subjects who received at least one dose of study drug and who had baseline assessments of polyp size (nasoendoscopy) and recorded morning nasal congestion/obstruction symptoms.

A subject was considered eligible for surgical intervention if the following conditions were met: * Subject has had moderate symptoms of congestion from nasal polyposis for ≥ 3 months. * Subject continues to suffer from at least moderate symptoms despite use of topical steroids at conventional doses for ≥ 6 weeks. * Subject continues to suffer from at least moderate symptoms despite use (or previous use) of saline lavage for ≥ 6 weeks. * Subject has endoscopically visualized bilateral nasal polyposis of at least moderate severity (nasal polyp grading score ≥ 2 in at least 1 nostril).

Time frame: Week 16 of the double-blind treatment phase; Week 24 of the open-label extension phase

Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.

Patient Global Impression of Change; subject responses to the question: Since starting the study drug, how would you rate the change in your symptoms? Percentage includes patients who scored either very much improved, much improved, or minimally improved.

Time frame: Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase

Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.

The PNIF is an assessment of nasal passage obstruction and was measured using an In-Check portable nasal inspiratory flow meter. To measure PNIF, a mask was placed over the nose during inspiration and inspiratory flow was recorded. Each subject inhaled 3 times and each measurement was recorded. The PNIF value used was the greatest of the 3 results at each time point. Change from baseline in Peak Nasal Inspiratory Flow (PNIF)

Time frame: Week 16 of the double-blind treatment phase; Week 24 of the open-label extension phase

Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.

Subjects with a Polyp Grade of 0 (None) in at least one nostril Polyp grading of each nasal cavity was determined by a nasal polyp grading scale score measured by nasoendoscopy. This outcome measured how many patients with a polyp grad of 0 in at least 1 nostril. 0: No polyps 1. Mild polyposis: polyps not reaching below the inferior border of the middle turbinate 2. Moderate polyposis: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate 3. Severe polyposis large polyps reaching below the lower inferior border of the inferior turbinate

Time frame: Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase

Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.

The RSDI is a subject-completed instrument that evaluates the self-perceived impact of disease specific head and neck disorders. The RSDI has 30 items in 3 domains: Physical (11 items), Functional (9 items), and Emotional (10 items). The RSDI scale ranges from 0-120, 0 being better quality of life and less impact of CRS on daily function and 120 being worse quality of life and more impact of CRS on daily function.

Time frame: Baseline, Week 16 of the double-blind treatment phase

The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.

Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase

Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.

The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire that measures 8 domains of health: limitations in physical activities, limitations in social activities, limitations in usual role activities, bodily pain, general mental health, limitations in usual role activities, vitality, and general health perceptions. It yields scale scores for each of the 8 health domains, and 2 summary measures of physical and mental health. Each scale range is from 0-100. A lower score means more disability and a higher score means less disability.

Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase

Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.

SNOT-22 is a subject-completed questionnaire that consists of 22 questions. The questions on the SNOT-22 efficacy evaluation were used to calculate a total score. 22 questions are divided among 4 subscales: Rhinologic (7 questions), Ear/Facial Symptoms (4 questions), Sleep Function (3 questions), and Psychological Issues (6 questions). Each item was rated on the 5-point scale. The total score can range from 0-110, 0 being the best and 110 being the worst. 0: No problem 1. Very mild problem 2. Mild or slight problem 3. Moderate problem 4. Severe problem 5. Problem as bad as it can be

Time frame: Baseline, Week 16 of the double-blind treatment phase, Week 24 of the open-label extension phase

Population: Number of patients analyzed at Week 24 is lower as some patients elected not to participate in the open-label extension phase or withdrew during the open-label extension phase.